7-116576975-T-C

Variant names:

• chr7-116576975-T-C
• rs7795356
• ENST00000441991.2:n.188-3231A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000450063.2(COMETT):​n.546-3231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,158 control chromosomes in the GnomAD database, including 48,886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (48886 hom., cov: 33)
• Consequence: COMETT ENST00000450063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• Publications: 4 publications found

Genes affected

COMETT (HGNC:51196): (cytosolic oncogenic antisense to MET transcript) This gene encodes a natural antisense transcript highly expressed in papillary thyroid carcinomas harboring BRAF V600E mutation or RET gene rearrangements. This lncRNA induces the downstream MAPK pathway and is part of a co-expression network including different oncogenes belonging to the MAPK and PI3H/AKT pathways. In thyroid carcinomas, this gene has oncogenic properties associated with increased proliferation and drug resistance. [provided by RefSeq, Jan 2020]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000450063.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMETT	NR_120506.2		n.204-3231A>G		intron	N/A
	COMETT	NR_165032.1		n.391-5745A>G		intron	N/A
	COMETT	NR_165033.1		n.391-3231A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMETT	ENST00000441991.2	TSL:3	n.188-3231A>G		intron	N/A
	COMETT	ENST00000450063.2	TSL:2	n.546-3231A>G		intron	N/A
	COMETT	ENST00000458082.2	TSL:3	n.367-3231A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121781 AN: 152040 Hom.: 48848 Cov.: 33

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.795

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.801 AC: 121880 AN: 152158 Hom.: 48886 Cov.: 33 AF XY: 0.805 AC XY: 59853 AN XY: 74396

African (AFR) AF: 0.750 AC: 31120 AN: 41484

American (AMR) AF: 0.845 AC: 12907 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2864 AN: 3470

East Asian (EAS) AF: 0.946 AC: 4900 AN: 5182

South Asian (SAS) AF: 0.810 AC: 3904 AN: 4822

European-Finnish (FIN) AF: 0.829 AC: 8785 AN: 10598

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54784 AN: 68004

Other (OTH) AF: 0.796 AC: 1682 AN: 2114

Alfa AF: 0.806 Hom.: 148031

Bravo AF: 0.802

Asia WGS AF: 0.865 AC: 3009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.77
PhyloP100		-0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7795356; hg19: chr7-116217029; COSMIC: COSV71451730;